: It was recently discovered that reduced ETC signaling in neuronal cells is sufficient to extend the lifespan of C. elegans. It was also found that this effect is dependent upon the activity of an essential component of the mitochondrial stress response or UPRmt. It is not yet understood, however, the fundamental mechanisms by which this life span extension occurs or how the signal is sent and perceived. Moreover, the essential role that the mitochondrion has in cellular homeostasis and energy production suggests that it may act as a reactive sensor of random intrinsic or extrinsic variables capable of influencing an organism's susceptibility to disease. Changes within the mitochondria thus also might be responsible for the emergent properties displayed in such a system in response to stochastic changes, and/or may play a significant role in coordinating the activation of non-mitochondrial stress response pathways. A prediction that genetic modifications will decrease the capacity for stochastic variation in mitochondrial function will ultimately negatively affect the fitness of the organism. Such a hypothesis is in keeping with recent evidence suggesting that deleterious mutations actually decrease the sensitivity of gene expression in response to small environmental changes (a loss of phenotypic robustness). A further hypothesis is it may predict co-variance between the UPRmt and stress response pathways, currently thought to act in distinct regulatory networks, and seek to discover the potential mechanisms by which this co-variance occurs.